The cholesterol concentration in the plasma membranes of cultured normal cells or neoplastically transformed cells can be reduced by blocking cholesterol biosynthesis with any one of several oxygenated sterols. The effect of the depletion of cellular sterol on the biological functions of plasma membranes, e.g., transport of ions and nutrients, will be investigated. The mechanism of inhibition of cholesterol synthesis by oxygenated sterols will be studied using mutant cells which are resistant to 25-hydroxycholesterol. The relationship between sterol synthesis and cell proliferation in synchronized normal and transformed cell cultures and in lymphocytes and leukemic cells will be analyzed.